Wallmann Tatjana, Zhang Xing-Mei, Wallerius Majken, Bolin Sara, Joly Anne-Laure, Sobocki Caroline, Leiss Lina, Jiang Yiwen, Bergh Jonas, Holland Eric C, Enger Per Ø, Andersson John, Swartling Fredrik J, Miletic Hrvoje, Uhrbom Lene, Harris Robert A, Rolny Charlotte
Karolinska Institutet, Department of Oncology-Pathology, CCK, R8:01, 171 76 Stockholm, Sweden.
Karolinska Institutet, Department of Clinical Neuroscience, Karolinska Hospital at Solna, CMM, 171 76 Stockholm, Sweden.
iScience. 2018 Nov 30;9:71-83. doi: 10.1016/j.isci.2018.10.011. Epub 2018 Oct 16.
High-grade gliomas (HGGs) are the most aggressive and invasive primary brain tumors. The platelet-derived growth factor (PDGF) signaling pathway drives HGG progression, and enhanced expression of PDGF receptors (PDGFRs) is a well-established aberration in a subset of glioblastomas (GBMs). PDGFRA is expressed in glioma cells, whereas PDGFRB is mostly restricted to the glioma-associated stroma. Here we show that the spatial location of TAMMs correlates with the expansion of a subset of tumor cells that have acquired expression of PDGFRB in both mouse and human low-grade glioma and HCGs. Furthermore, M2-polarized microglia but not bone marrow (BM)-derived macrophages (BMDMs) induced PDGFRB expression in glioma cells and stimulated their migratory capacity. These findings illustrate a heterotypic cross-talk between microglia and glioma cells that may enhance the migratory and invasive capacity of the latter by inducing PDGFRB.
高级别胶质瘤（HGGs）是最具侵袭性的原发性脑肿瘤。血小板衍生生长因子（PDGF）信号通路驱动HGG进展，而血小板衍生生长因子受体（PDGFRs）的表达增强是胶质母细胞瘤（GBMs）亚群中一种公认的异常现象。血小板衍生生长因子受体α（PDGFRA）在胶质瘤细胞中表达，而血小板衍生生长因子受体β（PDGFRB）大多局限于胶质瘤相关基质。在此我们表明，肿瘤相关巨噬细胞（TAMMs）的空间位置与在小鼠和人类低级别胶质瘤及高级别胶质瘤中获得PDGFRB表达的一部分肿瘤细胞的扩增相关。此外，M2极化的小胶质细胞而非骨髓（BM）来源的巨噬细胞（BMDMs）诱导胶质瘤细胞中PDGFRB表达并刺激其迁移能力。这些发现说明了小胶质细胞与胶质瘤细胞之间的异型串扰，这可能通过诱导PDGFRB来增强后者的迁移和侵袭能力。
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